Exchange of iron in the body

Normally, the body of an adult healthy person contains about 3-5 g of iron, so iron can be classified as trace elements. Iron is distributed unevenly in the body. Approximately 2/3 of the iron is contained in the hemoglobin of erythrocytes - it is a circulating iron pool (or pool). In adults, this pool is 2-2.5 g, in full-term newborns - 0.3-0.4 g, and in preterm infants - 0.1-0.2 g. Relatively much iron is contained in myoglobin: 0.1 g - in men and 0.05-0.07 g - in women. In the human body contains more than 70 proteins and enzymes, which include iron (for example, transferrin, lactoferrin), the total amount of iron in them is 0,05-0,07 g. Iron, transported by transport protein transferrin, is about 1% ( transport fund of iron). For medical practice, iron reserves (depot, reserve fund), which account for about 1/3 of the total iron in the human body, are extremely important. The following bodies perform the function of the depot:

• liver;
• spleen;
• Bone marrow;
• brain.

Iron is contained in the depot in the form of ferritin. The amount of iron in the depot can be characterized by determining the concentration of SF. To date, SF is the only internationally recognized marker of iron reserves. The final product of the exchange of iron is hemosiderin deposited in tissues.

Iron - the most important cofactor of the enzymes of the mitochondrial respiratory chain, citrate cycle, DNA synthesis, it plays an important role in the binding and transport of oxygen by hemoglobin and myoglobin; proteins containing iron are necessary for the metabolism of collagen, catecholamines, tyrosine. Due to the catalytic action of iron in the reaction Fe ² * <-> Fe ³, free uncheated iron forms hydroxyl radicals, which can cause damage to cell membranes and cell death. In the course of evolution, protection against the damaging effect of free iron was solved by the formation of specialized molecules for the absorption of iron from food, its absorption, transport and deposition in a non-toxic soluble form. Transport and deposition of iron are carried out by special proteins: transferrin, transferrin receptor, ferritin. The synthesis of these proteins is regulated by a special mechanism and depends on the needs of the organism.

[1], [2], [3], [4]

Metabolism of iron in a healthy person is closed in a cycle

Every day, a person loses about 1 mg of iron with biological fluids and a slackened epithelium of the digestive tract. Exactly the same amount can be absorbed into the digestive tract from food. It should be clear that iron enters the body only with food. Thus, every day 1 mg of iron is lost and 1 mg is absorbed. In the process of destruction of old erythrocytes, iron is released, which is utilized by macrophages and is again used in the construction of heme. In the body there is a special mechanism of iron absorption, but it is withdrawn passively, that is, there is no physiological mechanism for excretion of iron. Consequently, if the absorption of iron from food does not satisfy the needs of the body, iron deficiency occurs irrespective of the cause.

Distribution of iron in the body

1. 70% of the total amount of iron in the body is part of the hemoproteins; these are compounds in which iron is bound to porphyrin. The main representative of this group is hemoglobin (58% of iron); In addition, this group includes myoglobin (8% iron), cytochrome, peroxidase, catalase (4% iron).
2. A group of non-heme enzymes - xanthine oxidase, NADH dehydrogenase, aconitase; these iron-containing enzymes are localized mainly in the mitochondria, play an important role in the process of oxidative phosphorylation, transport of electrons. They contain very little metal and do not affect the overall balance of iron; However, their synthesis depends on the provision of tissues with iron.
3. The transport form of iron is transferrin, lactoferrin, a low-molecular-weight iron carrier. The main transport plasma ferroprotein is transferrin. This beta-globulin fraction protein with a molecular weight of 86,000 has 2 active sites, each of which can attach one Fe ³⁺ atom at a time . In plasma there are more iron-binding sites than iron atoms and, thus, there is no free iron in it. Transferrin can bind other metal ions - copper, manganese, chromium, but with a different selectivity, and iron binds first and more firmly. The main site of transferrin synthesis is liver cells. With the increase in the level of deposited iron in hepatocytes, the synthesis of transferrin is markedly reduced. Transferrin, carrying iron, aviden to normocytes and reticulocytes, and the amount of metal uptake depends on the presence of free receptors on the surface of erythroid progenitors. On the membrane of the reticulocyte, there are significantly fewer binding sites for transferrin than on the prothromocyte, that is, as the erythroid cell ages, the capture of iron decreases. Low-molecular-weight iron carriers provide iron transport inside the cells.
4. Deposited, reserve or reserve iron can be in two forms - ferritin and hemosiderin. The reserve iron compound consists of an apoferritin protein, the molecules of which surround a large number of iron atoms. Ferritin - a brown compound, soluble in water, contains 20% iron. With excessive accumulation of iron in the body, ferritin synthesis increases dramatically. Ferritin molecules exist in almost all cells, but especially in the liver, spleen, and bone marrow. Hemosiderin is present in the tissues in the form of a brown, granular, water-insoluble pigment. The iron content in hemosiderin is higher than in ferritin - 40%. Damaging effect of hemosiderin in tissues is associated with damage to lysosomes, accumulation of free radicals, which leads to cell death. In a healthy person, 70% of the reserve iron is in the form of ferritin, and 30% in the form of hemosiderin. The rate of hemosiderin use is much lower than that of ferritin. The iron stores in tissues can be judged on the basis of histochemical studies, applying the semi-quantitative method of evaluation. Count the number of sideroblasts - nuclear erythroid cells containing different amounts of non-heme iron granules. A feature of the distribution of iron in the body of young children is that they have a higher iron content in erythroid cells and less iron is on muscle tissue.

Regulation of iron balance is based on the principles of almost complete reutilization of endogenous iron and maintenance of the required level due to absorption in the gastrointestinal tract. The half-life of iron removal is 4-6 years.

[5], [6], [7], [8], [9], [10], [11], [12], [13], [14],

Absorption of iron

Absorption occurs mainly in the duodenum and the initial part of the jejunum. With a deficiency of iron in the body, the suction zone spreads distally. In a daily diet usually contains about 10-20 mg of iron, but only 1-2 mg is absorbed in the gastrointestinal tract. Absorption of heme iron greatly exceeds the flow of inorganic iron. Regarding the influence of iron valence on its absorption in the gastrointestinal tract, there is no unequivocal opinion. VI Nikulicheva (1993) believes that Fe ^{2+ is} practically not absorbed either under normal or excessive concentrations. According to other authors, iron absorption is not dependent on its valence. It was found that the valence of iron, and its solubility in the duodenum in alkaline reaction, is of decisive importance. Gastric juice and hydrochloric acid are involved in the absorption of iron, provide the reduction of the oxide form (Fe ^H ) in the expressed (Fe ²⁺ ), ionization, the formation of components accessible to absorption, but this only applies to the non-heme gland and is not the main mechanism of absorption regulation.

The process of absorption of heme iron does not depend on gastric secretion. Hem iron is absorbed in the form of a porphyrin structure and only in the mucous membrane of the gut is its cleavage from the heme and the formation of ionized iron. Iron is better absorbed from meat products (9-22%) containing heme iron, and much worse - from plant (0.4-5%), where there is non-heme iron. Of the meat products, iron is assimilated in different ways: iron is absorbed from the liver worse than from meat, since in the liver, iron is contained in the form of hemosiderin and ferritin. Boiling vegetables in large amounts of water can reduce the iron content by 20 %.

Unique is the absorption of iron from breast milk, although its content is low - 1.5 mg / l. In addition, breast milk increases the absorption of iron from other foods consumed simultaneously with it.

In the process of digestion, iron enters the enterocyte, from where it passes through the concentration gradient into the blood plasma. With a deficiency of iron in the body, its transfer from the lumen of the gastrointestinal tract to the plasma is accelerated. With an excess of iron in the body, the bulk of the iron lingers in the cells of the intestinal mucosa. The enterocyte laden with iron moves from the base to the top of the villi and is lost with the depleted epithelium, which prevents the excessive intake of metal into the body.

The process of iron absorption in the gastrointestinal tract is affected by various factors. The presence of oxalates, phytates, phosphates, tannin in the bird reduces the absorption of iron, as these substances form complexes with iron and remove it from the body. On the contrary, ascorbic, succinic and pyruvic acids, fructose, sorbitol, alcohol increase the absorption of iron.

In plasma, iron binds to its carrier - transferrin. This protein transports iron mainly to the bone marrow, where iron penetrates into erythrocaryocytes, and transferrin returns to plasma. Iron enters the mitochondria, where heme synthesis takes place.

The further path of iron from the bone marrow can be described as follows: with physiological hemolysis from erythrocytes, 15-20 mg of iron per day is released, which is utilized by phagocytic macrophages; then most of it goes back to hemoglobin synthesis and only a small amount remains as a spare gland in macrophages.

30% of the total iron content in the body is used not for erythropoiesis, but is deposited in the depot. Iron in the form of ferritin and hemosiderin is stored in parenchymal cells, mainly in the liver and spleen. Unlike macrophages, the parenchymal cells use iron very slowly. The intake of iron into the parenchymal cells increases with a significant excess of iron in the body, hemolytic anemia, aplastic anemia, renal insufficiency and decreases with a pronounced deficit of the metal. The release of iron from these cells increases with bleeding and decreases with blood transfusions.

The overall pattern of iron metabolism in the body will be incomplete if we do not take into account the tissue iron. The amount of iron that is part of ferroenzymes is small - only 125 mg, but the importance of tissue respiration enzymes can not be overestimated: without them, the life of any cell would be impossible. The stock of iron in cells allows to avoid the direct dependence of the synthesis of iron-containing enzymes on the fluctuations of its intake and expenditure in the body.

[15], [16], [17], [18], [19]

Physiological losses and peculiarities of iron metabolism

Physiological loss of iron from the body in an adult is about 1 mg per day. Iron is lost along with peeling skin epithelium, epidermal appendages, then, with urine, feces, with sluschivayuschimsya intestinal epithelium. Women, in addition, are joined by the loss of iron with blood during menstruation, during pregnancy, childbirth, lactation, which is about 800-1000 mg. The exchange of iron in the body is presented in Scheme 3. It is interesting to note that the iron content in the serum and transferrin saturation vary within a day. Observe high serum iron concentrations in the morning and low values in the evening. Deprivation of sleep people leads to a gradual decrease in the iron content in the serum.

Metabolism of iron in the body is affected by trace elements: copper, cobalt, manganese, nickel. Copper is necessary for the assimilation and transport of iron; its effect is through cytochrome oxidase, ceruloplasmin. The action of manganese on the process of hematopoiesis is non-specific and is associated with its high oxidative ability.

To understand why iron deficiency is most common in young children, adolescent girls and women of childbearing age, we will consider the features of iron metabolism in these groups.

The accumulation of iron in the fetus occurs throughout the entire pregnancy, but most intensively (40%) in the last trimester. Therefore, prematurity in 1-2 months leads to a reduction in iron availability by a factor of 1.5-2 compared to full-term children. It is known that the fetus has a positive balance of iron, which goes against the concentration gradient in favor of the fetus. The placenta more intensively captures iron than the bone marrow of a pregnant woman, and has the ability to metabolize iron from the mother's hemoglobin.

The effect of iron deficiency in the mother on the stocks of this microelement in the fetus is inconsistent. Some authors believe that the sideropenia of a pregnant woman does not affect the iron stores of the fetus; others believe that there is a direct dependence. We can assume that with a decrease in the iron content in the mother's body, a deficit of iron stores in the newborn develops. However, the development of iron deficiency anemia due to congenital iron deficiency is unlikely, since the frequency of development of iron deficiency anemia, hemoglobin level and serum iron in the first 24 hours after birth and in the next 3-6 months do not differ in children born from healthy mothers and mothers with iron deficiency anemia. The iron content in the body of the newborn full-term and premature baby is 75 mg / kg.

In children, unlike adults, alimentary iron should not only make up for the physiological losses of this trace element, but also provide for growth needs, which averages 0.5 mg / kg per day.

Thus, the main prerequisites for the development of iron deficiency in premature infants, children from multiple pregnancy, children under 3 years are:

• rapid depletion of stocks with insufficient exogenous intake of iron;
• increased need for iron.

Iron metabolism in adolescents

The peculiarity of iron metabolism in adolescents, especially in girls, is a pronounced discrepancy between the increased need for this trace element and its low intake into the body. The reasons for this discrepancy are: rapid growth, poor nutrition, exercise, abundant menstruation, the initial low iron level.

In women of childbearing age, the main factors leading to the development of iron deficiency in the body are abundant and prolonged menstruation, multiple pregnancies. The daily need for iron in women who lose 30-40 ml of blood for menstruation, is 1.5-1.7 mg / day. With a greater loss of blood, the need for iron increases to 2.5-3 mg / day. In fact, only 1.8-2 mg / day can be delivered via the gastrointestinal tract, that is, 0.5-1 mg / day of iron can not be replenished. Thus, within a month the micronutrient deficiency will amount to 15-20 mg, 180-240 mg per year, 1.8-2.4 g for 10 years, that is, this deficiency exceeds the content of spare iron in the body. In addition, for the development of iron deficiency in women, the number of pregnancies, the interval between them, the duration of lactation are important.